Modulation of Structure and Dynamics of Cardiac Troponin by Phosphorylation and Mutations Revealed by Molecular Dynamics Simulations.

ABSTRACT: Adrenaline acts on β1 receptors in the heart muscle to enhance contractility, increase the heart rate, and increase the rate of relaxation (lusitropy) via activation of the cyclic AMP-dependent protein kinase, PKA. Phosphorylation of serines 22 and 23 in the N-terminal peptide of cardiac troponin I is responsible for lusitropy. Mutations associated with cardiomyopathy suppress the phosphorylation-dependent change. Key parts of troponin responsible for this modulatory system are disordered and cannot be resolved by conventional structural approaches. We performed all-atom molecular dynamics simulations (5 × 1.5 μs runs) of the troponin core (419 amino acids) in the presence of Ca²⁺ in the bisphosphorylated and unphosphorylated states for both wild-type troponin and the tro

SUBMITTER: Yang Z 

PROVIDER: S-EPMC10591477 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature